ABSTRACT
BACKGROUND: Maximum skin hyperaemia (MH) induced by heating skin to > or = 42 degrees C is impaired in individuals at risk of diabetes and cardiovascular disease. Interpretation of these findings is hampered by the lack of clarity of the mechanisms involved in the attainment of MH. METHODS: MH was achieved by local heating of skin to 42-43 degrees C for 30 min, and assessed by laser Doppler fluximetry. Using double-blind, randomized, placebo-controlled crossover study designs, the roles of prostaglandins were investigated by inhibiting their production with aspirin and histamine, with the H1 receptor antagonist cetirizine. The nitric oxide (NO) pathway was blocked by the NO synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME), and enhanced by sildenafil (prevents breakdown of cGMP). RESULTS: MH was not altered by aspirin, cetirizine or sildenafil, but was reduced by L-NAME: median placebo 4.48 V (25th, 75th centiles: 3.71, 4.70) versus L-NAME 3.25 V (3.10, 3.80) (p = 0.008, Wilcoxon signed rank test). Inhibition of NO production (L-NAME) resulted in a more rapid reduction in hyperaemia after heating (p = 0.011), whereas hyperaemia was prolonged in the presence of sildenafil (p = 0.003). The increase in skin blood flow was largely confined to the directly heated area, suggesting that the role of heat-induced activation of the axon reflex was small. CONCLUSION: NO, but not prostaglandins, histamine or an axon reflex, contributes to the increase in blood flow on heating and NO is also a component of the resolution of MH after heating.
Subject(s)
Hot Temperature , Hyperemia/metabolism , Nitric Oxide/metabolism , Skin/metabolism , Aspirin/pharmacology , Cetirizine/pharmacology , Cross-Over Studies , Cyclic GMP/metabolism , Cyclooxygenase Inhibitors/pharmacology , Double-Blind Method , Female , Histamine/metabolism , Histamine H1 Antagonists, Non-Sedating/pharmacology , Humans , Hyperemia/diagnostic imaging , Laser-Doppler Flowmetry , Male , Microcirculation , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Phosphodiesterase Inhibitors/pharmacology , Piperazines/pharmacology , Prostaglandins/metabolism , Purines , Reference Values , Regional Blood Flow/drug effects , Sildenafil Citrate , Skin/blood supply , Skin/diagnostic imaging , Skin/drug effects , Sulfones , UltrasonographyABSTRACT
It is hypothesised that vascular dysfunction, which characterises type 2 diabetes, may predate development of hyperglycaemia. 17 women with previous gestational diabetes mellitus, and thus at risk of developing type 2 diabetes, were matched with normal controls for body mass index, menstrual phase, smoking, age, blood pressure, and lipid profiles. All had normal glucose tolerance. Tests of microvascular and macrovascular function, including endothelium-dependent and -independent vasodilatation, were performed. Laser Doppler fluximetry of maximum skin microvascular hyperaemia in response to local heating of the dorsum of the foot to 42 degrees C for 30 min was impaired in subjects compared to controls [subjects = 1.15 (0.73-1.73) V median (range) versus controls = 1.50 (0.95-2.29) V, p = 0.008]. There were no differences in laser Doppler perfusion imaging of responses to forearm skin iontophoresis of acetylcholine [subjects = 1.59 (0.32-2.55) V median (range) versus controls = 1.79 (0.72-2.06) V; p = 0.81] and sodium nitroprusside [subjects = 1.39 (0.8-3.14) V versus controls = 1.41 (0.34-2.19) V; p = 0.68], ultrasound estimation of brachial artery flow-mediated dilatation [subjects = 1.65 (-0.5-9.07)% versus controls = 2.77 (0.63-6.6)%; p = 0.42] and glyceryl trinitrate-induced dilatation [subjects = 15.20 (6.64-20.91)% versus controls = 15.92 (3.94-22.09)%; p = 0.48]. Microvascular maximum hyperaemia was impaired in the index group, suggesting the presence of a defect in vascular function. This defect was not explained by those aspects of endothelial function measured by the other techniques.
